What started out as another quiet day in paradise turned into a rolling parade of shocks and minor surprises: Novak Djokovic beaten for only the second time in 30 matches this year, and Aljaz Bedene targeting Rafael Nadal’s once-feared forehand on clay, before losing anyway.

Elsewhere, Maria Sharapova was left in legal limbo about making a comeback, thanks to a barely comprehensible statement from the World Anti-Doping Agency that at first suggested she might be granted a reprieve for failing a drugs test at the Australian Open. However, she has yet to establish when she took the banned drug meldonium and in what strength. Lawyers are consulting.

By the Mediterranean, Djokovic, the world No1 with a grip on the game as tight as a boa constrictor, leaves a tournament earlier than he has done since the second round in Madrid three years agoin 2013, after Jiri Vesely, 55 in the world, produced the performance of his short career to win 6-4, 2-6, 6-4, his first victory over a top-10 player in nine attempts.

Fighting hard for every point in the afternoon sun, Vesely served for their second-round match after two hours. An outrageous dropshot from the baseline helped him on his way and the joy on his face when the Serb’s final forehand drifted long was a picture Caravaggio might have painted.

The 22-year-old Czech now takes Djokovic’s all-but-nailed-on place at the top end of the draw. The Serb’s earlier defeat this year was an injury retirement when trailing Feliciano López 3-6 in Dubai. His last genuine loss was in Cincinnati last year when Roger Federer, charging the net like an excitable youth, took him out in two sets in the final. “Nobody’s unbeatable,” the surprisingly upbeat loser said. “I was playing really, really bad. Bad footwork. But I have to congratulate my opponent.

“He played very solid. He was serving very big. He was playing tactically good and aggressive. When he was break up in the third set, he was playing bravely. He was coming in, dropshots, big serves. He was going for it. He deserved to have it.”

The now-no-longer defending champion returned to his home here 10 days ago to prepare, so could not complain about lack of practice – although he has been busy off-court too, and entertained friends and some players, including Andy Murray, at the opening of his new restaurant on Sunday night.

He nonetheless will put the setback behind him and remains upbeat about his chances of winning the one slam that has eluded him, the French Open, which starts next month.

But what of the one-time king of that tournament, Nadal? If Murray plays the Spaniard in the semi-finals here, he is likely to encounter a considerably less threatening opponent than the one who strung together eight consecutive Monte Carlo titles.

The Scot first has to get past the Frenchman Benoît Paire on Thursday – with Tomas Berdych a surprise loser in his section of the draw on Tuesday, and Milos Raonic still a potential roadblock – but he will be encouraged by Nadal’s sub-standard win against Bedene.

Nadal spent only an hour and 19 minutes beating Bedene 6-3, 6-3 on Court Rainier III but he struggled at key moments, looking laboured in the shot and generally out of sorts.

What stunned the Spaniard was the British No2’s nagging attack to his own forehand, once considered tennis suicide. But, as Bedene explained later, “I didn’t play my best tennis. And seeing him struggling on the forehand side, I was trying to change a bit because I know, like, a few years ago when he was ripping his forehand, that was his best shot. But now when you press his forehand, that’s his weaker side.”

It is inconceivable anyone would have uttered those words even a couple of years ago but it is plain that Nadal at 30 is in a real fight to turn his career around after so many years alongside Federer, Djokovic and Murray.

Bedene added: “I wasn’t feeling great. Got injections in my back in the morning because couldn’t do much without [them]. At the beginning I was struggling a bit. He was playing decent ball. His spin gets you way back. But from 1-5 down, I was playing my tennis, got into the match. I had a breakback point for 4-5. I didn’t use it, didn’t play to capacity. I knew he was struggling there. If I had broken there, it would have been interesting.”

It was anyway, for all sorts of reasons. It is not often you see two giants of the era in trouble on the same day. Now the door is ajar for Murray. He has never played Paire but he always does his homework.

Raonic, who took three sets to beat Pablo Cuevas in two hours and 35 minutes still ought to have enough left to get past the 23-year-old Bosnian Damir Dzumhur, who beat Berdych 6-4, 6-7 (1-7), 6-3 in about the same time. Nadal plays the exciting Dominic Thiem, who recovered from a slow start to overwhelm Japan’s Taro Daniel in three sets.